This document discusses antioxidants and free radicals. It defines free radicals as highly reactive oxygen molecules that can damage cells. Antioxidants prevent this damage by slowing or inhibiting oxidation reactions. The summary describes the main types of antioxidants like vitamins C and E, glutathione, minerals, and enzymes like superoxide dismutase that protect against free radicals. It also summarizes the mechanisms of antioxidant action and their clinical significance in reducing disease risks.
5. Reactive oxygen species (ROS)
● Defined as all highly unstable and highly reactive oxygen
containing molecules including free radicals
● Capable of reacting with membrane lipids, nucleic acids,
proteins and enzymes resulting in cellular damage
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7. In vivo production of ROS & free radicals
● O2
- and H2O2 by
○ Activated phagocytes
○ Endothelial cells
○ Fibroblasts and lymphocytes
○ Auto oxidation reactions
○ Leakage of electrons from
the electron transport chains
● NO- by
○ Vascular endothelial cells
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8. Free radicals – physiological roles
● O2- inactivates enzymes in bacteria in vitro, inactivates NADH
dehydrogenase complex in the mitochondrial electron transport
chain
● NO- (or a derivative) smooth muscle cell relaxation
● O2- + NO- peroxynitrite (ONOO-) vasoconstriction
(regulation of vascular tone)
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15. MODES OF ACTION OF ANTIOXIDANT
● Chain breaking reactions
Ex : α tocopherol which acts in lipid phase to trap the radical
● Reducing the concentration of reactive oxygen species
Ex : glutathione
● Scavenging initiating radicals
Ex : SOD which acts in aqueous phase to trap superoxide free radicals
● Chelating the transition metal catalysts
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22. SUPEROXIDE DISMUTASE (SOD)
● Metalloprotein
● Ubiquitously in all aerobic organisms
● More potent antioxidant
● Mainly targets superoxide anion(O2
-) and singlet oxygen(‘O2)
● Function : 2O2
- + 2H+ -------------------- H2O2 + O2
● Has many subgroups : SOD1, SOD2 & SOD3
SOD
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23. SOD - TYPES
SOD 1 :
•Present in cytoplasm
•Co-factors : Cu & Zn
•Important constituent
in apoptotic signaling
& Oxidative stress
•Role in degenerative
diseases, oldage and
carcinogenesis
SOD 2 :
•Present in
mitochondria
•Co-factors : Fe & Mn
•Protects against cell
death due to oxidative
stress, ionizing radiation
and inflammatory
cytokines
SOD 3 :
•Extracellular
•Elimination has only
minimal effects
•Protects the brain,
lungs and other tissues
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24. GLUTATHIONE
● Mother of all antioxidants
● Hydrophilic ; found in every cells of the body
● “Directly found in cells and breakdown the free radicals within
the cells”
● Scavenges hydroxyl free radicals
● Sources : Garlic, Broccoli, Onions, Dairy products, Oats,
Chicken etc. 24
25. GLUTATHIONE
● Reduced form of glutathione :
○ Regulates IL2 dependent T lymphocyte proliferation
○ Reduce oxidative stress
○ Protects against cytotoxic effects of nicotine on fibroblasts
● Smoking – reduce glutathione in saliva & plasma
● Decrease the incidence of prostate, colon & lung cancer 25
26. VITAMINS - CAROTENES
● One of the essential antioxidant for health and well being
● Types : α, β, γ, δ – first two are most potent
● These are group of red, orange and yellow pigments found in
plant foods(fruits and vegetables)
● β Carotenes : anti-ageing micronutrients, decrease the immune
function, cardiac illnesses, cataract and cancer
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27. VITAMINS - TOCOPHEROL
● Also known as “vitamin E”
● α -tocopherol is an active form
● Fat soluble ; present in all cell membranes
● Mainly stored in adipose tissue, liver and muscle
● Sources : Peanut oil, Sunflower oil, Cotton seed oil and Green
leafy vegetables
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28. VITAMINS - TOCOPHEROL
● Prevents per oxidation at cell membranes and protects poly
unsaturated fats
● Enhances body’s immune responses
● Inhibits the conversion of nitrites into nitrosamines in stomach
(Nitrosamines – cancer promoters)
● Lowers the risk of angina and cardiac disease mortality
● Slows the progression of Parkinson's disease 28
29. VITAMINS – ASCORBIC ACID
● Vitamin C
● Water soluble ; secondary free radical scavenger
● Present in extra cellular fluids
● Mainly neutralizes H2O2
● Sources : Citrus fruits - lime, orange, tomatoes, amla &
cabbage, Watermelon etc.
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30. VITAMINS – ASCORBIC ACID
● Protecting tissues against oxidative stress
● Suppresses the formation of carcinogens
● Reduce the risk of cardiovascular diseases by decreasing total
cholesterol levels
● Maintains healthy collagen in skin, tissues and teeth etc.
● Reduced levels of vitamin C can cause cataract
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31. MINERALS
● Works along with vitamins in fighting free radicals
○ Ex : Vitamin E + Selenium free radical scavenging
● Act as enzyme co-factors
○ Zinc & Copper – for SOD1 & Iron & Mn – for SOD2
● Selenium : reduces colorectal, prostate and lung cancers
● Zinc + vitamin A synergistic action persistent diarrhoea
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32. PROTEINS
● Ceruloplasmin & Transferrin – prevents iron dependent lipid
peroxidation
● Bilirubin – protects albumin bound free fatty acids from
peroxidation
● Albumin – scavenges the free radicals which binds on its
surface
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33. HORMONES - MELATONIN
● Powerful antioxidant
● Can cross blood brain barrier and other cell membranes
● Binds with free radicals forms stable complex “Terminal
/ Suicidal antioxidant”
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34. URIC ACID
● Most abundant ; Uncomplicated antioxidant
● Marker of oxidative stress
● More potent against singlet oxygen and hydroxyl radicals
● Sources : sweetbread, liver, beef meat etc.
● Reduce the risk of stroke, atherosclerosis and Parkinson’s
disease.
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35. ESSENTIAL OILS
● Volatile oils
● Isolated from various plant components – leaves, flower etc.
● Advantages :
○ Small molecular size – easily penetrate skin tissues
○ Lipid soluble – Easily penetrate & cross membranes
○ Powerful antioxidant – prevent mutants and oxidants in cells 35
37. SUMMARY
● Oxidative reactions that releases the highly reactive free radicals
that causes cell damage
● Antioxidants acts on free radicals and prevents cell damage
● Endogenous antioxidants focusing on primary free radicals
● Exogenous antioxidants obtained mainly from natural & dietary
sources and targets secondary free radicals
● SOD – Continuous elimination within the cell level 37
38. SUMMARY
● Glutathione – mother of all antioxidants
● Fat soluble vitamins – present in membranes and prevents lipid
peroxidation
● Water soluble vitamins – present in ECF and neutralizes H2O2
● Minerals – act as enzyme co factors
● Melatonin – suicidal antioxidant
● Uric acid – most abundant & more potent against both 1&2’ ROS38
